Development and optimization of a novel colonic drug delivery system using multiple coatings of aqueous polymethacrylates

The objective of this work was to develop a multi-unit colonic delivery system of a model drug having predictable release properties that has the potential to sustain drug release in the colon for about 12 h.; Pellets were prepared by powder layering of 5-aminosalicylic acid (5-ASA) on nonpareils (0.5–0.6 mm) in a conventional coating pan. Drug-layered pellets were coated with an inner layer of a combination of two pH-independent polymers Eudragit® RL and RS and an outer layer of a pH-dependent polymer, Eudragit FS. SEM pictures of the coated pellets showed the uniformity of both the inner and outer coatings. The release profile of 5-ASA was studied for 12 h in USP phosphate buffers pH 6.5, 7.0, and 7.5 after a simulated gastric pre-soak for 2 h in pH 1.2 media.; At pH 6.5, there was no drug release for 12 h. There was a sustained release of 5-ASA for over 12 h both at pH 7.0 and 7.5. The release rate was faster at pH 7.5 than at pH 7.0. The delivery system demonstrated its potential for colonic targeting by resisting drug release until pH 6.5 and the combination of Eudragit RL and RS in the inner coat proved successful for the sustained delivery of 5-ASA at the expected pH of the colon.; Central composite design was used to study the effect of three independent variables. The proportion of the more hydrophilic polymer Eudragit RL had the most significant effect on drug release—higher proportion gave faster release; the amount of inner and outer coat did not have a significant effect on the rate of drug release at either 6 or 12 h in the range studied. An optimum formulation that releases 50–65% drug in 6 h and 85–100% drug in 12 h contained 3% inner coat, 21% proportion of Eudragit RL in the inner coat, and 20% of outer coat. The results demonstrated the reliability of the model in the preparation of coated pellets having predictable drug release for colonic delivery of 5-ASA.; Potential interactions between anionic (Eudragit FS) and cationic (Eudragit RL) polymers were studied. No evidence of physical or chemical interactions was found using DSC, NMR, and FT-IR.